The program involves three major research areas: Project I. The Mechanism of Bone Resorption and Formation. Attempts will be made to isolate and characterize both the high and low-molecular weight bone resorption-stimulating factors from human gingival tissues using gingival fragment cultures and monolayer cultures. Special attention will be paid to the presence and role of prostaglandin E2 and its precursors as well as the phosphodiesterase inhibitors. The mechanism of action of various bone resorption-stimulating factors will be explored, using the HSDM1 tumor and cell culture systems as models for studies of new stimulators and inhibitors of prostaglandin synthesis. Project II. Bone Collagen Metabolism. A sufficient amount of purified mouse bone collagenase will be prepared in order to study further the mechanism of action, the characteristics and chemical nature of the enzyme and to prepare antiserum to mouse bone collagenese for fluorescent antibody localization of the enzyme in bones. Quantitative and qualitative biochemical examination of new bone collagen formed in the presence of active bone resorption-stimulating factors will be undertaken. Project III. A Pharmacological Approach to the Treatment of the Periodontal Syndrome. Based on the ability of aspirin to block prostaglandin synthetase and inhibit bone resorption in tissue culture, and the ability of tetracycline to alter the microbial flora at the bottom of deep periodontal pockets, each of these agents will be tested in old beagles over a period of several years to determine whether they inhibit the progress of alveolar bone destruction.